Role of Osteoclast Regulation in Arthritis – A Review

Abstract

Osteoclasts are multinucleated bone degrading cells that differentiate from monocyte/macrocphage precursors of the hematopoietic system. From the bone marrow, precursors of osteoclasts move towards the systemic circulation through the attraction towards chemokines in the blood and are later taken up by various resorption sites where they undergo differentiation into osteoclasts. Macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-ҡB ligand (RANKL) play a pivotal role in the differentiation and activation of osteoclasts. M-CSF induces the expression of RANK on myeloid progenitors and RANKL activates its receptor to initiate osteoclast differentiation. RANKL also stimulates bone resorption in mature osteoclasts. Rheumatoid arthritis is an autoimmune disease that leads to severe bone destruction mediated by the abnormal activation of osteoclasts. Synovial tissues in rheumatoid arthritis produce inflammatory cytokines that act on osteoclast precursor cells, thereby differentiating them into osteoclasts by cooperating with RANKL. Bone resorption proceeds uncontrollably through the abnormal activity of osteoclasts, leading to bone and cartilage destruction in the joints. The involvement of osteoclasts in the pathogenesis of rheumatoid arthritis has been further confirmed through animal model studies.